Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1003177
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dc.titleSequencing of Pax6 Loci from the Elephant Shark Reveals a Family of Pax6 Genes in Vertebrate Genomes, Forged by Ancient Duplications and Divergences
dc.contributor.authorRavi V.
dc.contributor.authorBhatia S.
dc.contributor.authorGautier P.
dc.contributor.authorLoosli F.
dc.contributor.authorTay B.-H.
dc.contributor.authorTay A.
dc.contributor.authorMurdoch E.
dc.contributor.authorCoutinho P.
dc.contributor.authorvan Heyningen V.
dc.contributor.authorBrenner S.
dc.contributor.authorVenkatesh B.
dc.contributor.authorKleinjan D.A.
dc.date.accessioned2019-11-06T09:28:05Z
dc.date.available2019-11-06T09:28:05Z
dc.date.issued2013
dc.identifier.citationRavi V., Bhatia S., Gautier P., Loosli F., Tay B.-H., Tay A., Murdoch E., Coutinho P., van Heyningen V., Brenner S., Venkatesh B., Kleinjan D.A. (2013). Sequencing of Pax6 Loci from the Elephant Shark Reveals a Family of Pax6 Genes in Vertebrate Genomes, Forged by Ancient Duplications and Divergences. PLoS Genetics 9 (1) : e1003177. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1003177
dc.identifier.issn15537390
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161630
dc.description.abstractPax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions. Here we provide evidence that the genomes of many other vertebrate species contain multiple Pax6 loci. We sequenced Pax6-containing BACs from the cartilaginous elephant shark (Callorhinchus milii) and found two distinct Pax6 loci. Pax6.1 is highly similar to mammalian Pax6, while Pax6.2 encodes a paired-less Pax6. Using synteny relationships, we identify homologs of this novel paired-less Pax6.2 gene in lizard and in frog, as well as in zebrafish and in other teleosts. In zebrafish two full-length Pax6 duplicates were known previously, originating from the fish-specific genome duplication (FSGD) and expressed in divergent patterns due to paralog-specific loss of cis-elements. We show that teleosts other than zebrafish also maintain duplicate full-length Pax6 loci, but differences in gene and regulatory domain structure suggest that these Pax6 paralogs originate from a more ancient duplication event and are hence renamed as Pax6.3. Sequence comparisons between mammalian and elephant shark Pax6.1 loci highlight the presence of short- and long-range conserved noncoding elements (CNEs). Functional analysis demonstrates the ancient role of long-range enhancers for Pax6 transcription. We show that the paired-less Pax6.2 ortholog in zebrafish is expressed specifically in the developing retina. Transgenic analysis of elephant shark and zebrafish Pax6.2 CNEs with homology to the mouse NRE/P? internal promoter revealed highly specific retinal expression. Finally, morpholino depletion of zebrafish Pax6.2 resulted in a "small eye" phenotype, supporting a role in retinal development. In summary, our study reveals that the pleiotropic functions of Pax6 in vertebrates are served by a divergent family of Pax6 genes, forged by ancient duplication events and by independent, lineage-specific gene losses. © 2013 Ravi et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjecttranscription factor PAX6
dc.subjectanimal cell
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectCallorhinchus milii
dc.subjectcontrolled study
dc.subjectembryo
dc.subjectembryo development
dc.subjectgene
dc.subjectgene duplication
dc.subjectgene expression
dc.subjectgene locus
dc.subjectgene sequence
dc.subjectgenetic analysis
dc.subjectgenetic code
dc.subjectgenetic conservation
dc.subjectgenetic variability
dc.subjectmicrophthalmia
dc.subjectmorphological trait
dc.subjectmouse
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectOryzias
dc.subjectPax6 gene
dc.subjectphenotype
dc.subjectpleiotropy
dc.subjectretina development
dc.subjectsequence homology
dc.subjectshark
dc.subjectspecies comparison
dc.subjectteleost
dc.subjecttransgenics
dc.subjectzebra fish
dc.subjectAnimals
dc.subjectEvolution, Molecular
dc.subjectEye Proteins
dc.subjectGene Duplication
dc.subjectGene Expression Regulation
dc.subjectGenetic Variation
dc.subjectGenome
dc.subjectHomeodomain Proteins
dc.subjectMice
dc.subjectPaired Box Transcription Factors
dc.subjectPromoter Regions, Genetic
dc.subjectRepressor Proteins
dc.subjectRetina
dc.subjectSequence Analysis, DNA
dc.subjectSharks
dc.subjectVertebrates
dc.subjectZebrafish
dc.typeArticle
dc.contributor.departmentMEDICINE
dc.contributor.departmentPAEDIATRICS
dc.description.doi10.1371/journal.pgen.1003177
dc.description.sourcetitlePLoS Genetics
dc.description.volume9
dc.description.issue1
dc.description.pagee1003177
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